Trabectedin Plus Olaparib in Metastatic or Advanced Sarcomas (TOMAS)

NCT02398058 | Completed Phase 1 DMC

• 2 other identifiers: TOMAS2013-003638-33
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1b, multi-site, open-label, non-randomized clinical trial evaluating the safety, tolerability, and pharmacokinetics of escalating doses of olaparib and trabectedin in patients with unresectable advanced/metastatic sarcomas. Patients will continue to be treated on this combination regimen in the absence of disease progression, intolerable toxicity or patient's decision.

Conditions

Soft Tissue Sarcoma; Bone Tumor

Keywords

trabectedin; olaparib; sarcoma; bone tumor

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose

  safety will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03

  from start up to 6 weeks

Secondary Outcomes (10)

• Best Overall Response

  baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years

• Clinical Benefit Rate

  baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years

• Growth Modulation Index

  baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years

• Overall Survival

  baseline and up to 2 years

• Duration of Tumor Response

  baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years

Study Arms (1)

Trabectedin plus olaparib

EXPERIMENTAL

All patients will be treated with trabectedin and olaparib in an open-label fashion. The dosage of the drugs at which each patient is treated depends on the dose level reached at the time of enrollment.

Drug: trabectedin; Drug: olaparib

Interventions

trabectedin DRUG

trabectedin will be administered in a 24-h continuous i.v. infusion every 3 weeks

Also known as: ET-743, Yondelis

Trabectedin plus olaparib

olaparib DRUG

olaparib will be administered in a continuous daily dose every 12 hours

Also known as: AZD-2281, Lynparza

Trabectedin plus olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• written informed consent
• histologically documented and not surgically resectable or metastatic sarcomas which progressed after first or further line treatments for relapsing disease
• Measurable disease as defined by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0/1. ECOG PS 2 are eligible if depends solely on orthopedic problems
• Estimated life expectancy of ≥ 4 months
• Age ≥18 years
• Adequate organ function: Hemoglobin \> 10.0 g/dl; Absolute neutrophil count (ANC) \>1,500/mm3; Platelet count \>= 100,000/μl; Total bilirubin \< 1.5 times the upper limit of normal (ULN); ALT and AST \< 2.5 x ULN (\< 5 x ULN for patients with liver involvement of their cancer); Alkaline phosphatase \< 2.5 x ULN; PT-INR/PTT \< 1.5 x ULN; Serum creatinine \< 1.5 x ULN or creatinine clearance ≥ 50 ml/min; Albumin \> 25 g/l; Creatine phosphokinase (CPK) \< 2.5 x ULN

You may not qualify if:

• Involvement in the planning and/or conduct of the study
• Previous enrolment in the present study
• Participation in another clinical study with an investigational product during the last month
• Persistent toxicities (≥CTCAE grade 2) with the exception of alopecia, caused by previous anticancer therapies
• Dementia or significantly altered mental status
• Patients with any severe and/or uncontrolled medical conditions
• HIV infection
• Active clinically serious infections (\> grade 2 NCI-CTCAE version 4.03).
• Active viral hepatitis (HBV or HCV infection)
• Symptomatic metastatic brain or meningeal tumors (unless the patient is \> 6 months from definitive therapy, does not require corticosteroid treatment, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry).
• Patients with seizure disorders requiring medication (such as steroids or anti-epileptics)
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days before the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 5 months after last dose of study drug
• Patients with evidence or history of bleeding diathesis
• Patients undergoing renal dialysis
• Patients unable to swallow oral medications

Sponsors & Collaborators

• Italian Sarcoma Group: lead
• PharmaMar: collaborator
• AstraZeneca: collaborator
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator

Study Sites (3)

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, 10060, Italy

Location

Istituti Ortopedici Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

Bologna, 40136, Italy

Location

Istituto Nazionale Tumori - Unit of Medical Oncology

Milan, 20133, Italy

Location

Related Publications (2)

• Grignani G, D'Ambrosio L, Pignochino Y, Palmerini E, Zucchetti M, Boccone P, Aliberti S, Stacchiotti S, Bertulli R, Piana R, Miano S, Tolomeo F, Chiabotto G, Sangiolo D, Pisacane A, Dei Tos AP, Novara L, Bartolini A, Marchesi E, D'Incalci M, Bardelli A, Picci P, Ferrari S, Aglietta M. Trabectedin and olaparib in patients with advanced and non-resectable bone and soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian Sarcoma Group. Lancet Oncol. 2018 Oct;19(10):1360-1371. doi: 10.1016/S1470-2045(18)30438-8. Epub 2018 Sep 11.

  PMID: 30217671 RESULT

• Vyse S, Thway K, Huang PH, Jones RL. Next-generation sequencing for the management of sarcomas with no known driver mutations. Curr Opin Oncol. 2021 Jul 1;33(4):315-322. doi: 10.1097/CCO.0000000000000741.

  PMID: 33927108 DERIVED

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms

Interventions

Trabectedin; olaparib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Giovanni Grignani, MD

  Italian Sarcoma Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2015
• First Posted: March 25, 2015
• Study Start: July 20, 2014
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 14, 2021

Record last verified: 2021-04

Locations

IT (3)